Kidney & Urinary Tract Neoplasms. Jaroslava Dušková Inst. Pathol.,1st Med. Faculty, Charles Univ. Prague

Transcription

1 Kidney & Urinary Tract Neoplasms Jaroslava Dušková Inst. Pathol.,1st Med. Faculty, Charles Univ. Prague

2 Kidney & Urinary Tract Neoplasms - contents Kidney cancer epidemiology clinical symptoms classification & characteristics of the most frequent representatives Urothelial neoplasms and precanceroses epidemiology clinical symptoms classification & characteristics of the most frequent representatives

3 Kidney Cancer 2% of the total human cancer burden, M:F 2:1, middle age preference for developed (industrialized) countries risk factors: TOBACCO SMOKING, OBESITY, cadmium exp. genetics: von Hippel-Lindau (VHL), MET gene, deletions

4 M:F 2:1 The highest incidence in the Czech Republic WHO 4th ed. 2016

5 Symptoms silent for a long time - discovered by chance hematuria, dull flank pain, abdominal mass, metastatic spread fever, polycytemia, paraneoplastic syndrome early hematogenic spread possible

6 WHO 4th ed. 2016

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8 Epithelial Neoplasms of the Pelvis Benign - papillomas Malignant - carcinomas papillocarcinomas squamous cell Urinary ways

9 Kidney Tumours Benign Borderline Malignant

10 Kidney Adenoma Definition changing: Formerly - diam mm, till 2016 less than 5 mm without a clear cell component tubulopapillary architecture lack of atypiae & mitoses 2016: 15 mm

11 Epithelial Kidney Tumours benign ADENOMAS M 8260/0 M 8290/0 papillary tubulopapillary (<15mm!) oncocytic (oncocytoma) M 8325/0 metanephric

12 Oncocytoma M8290/0 Kidney cortex may be multicentric and bilateral Macro tan with a central stellate scar Micro Elmi - eosinophillic granular cytoplasm bizarre nuclei mitochondria filling up the cytoplasm Biological behaviour benign

13 loss of chromosomes 1,14, y Oncocytoma renis

14 Oncocytoma renis

15 Kidney Tumours - mesenchymal Angiomyolipoma - mixed mesenchymal tumour ICD-O M 8860/0 sporadic or associated with tuberous sclerosis (TSC 1,2 genes 9q34) occasionally large & multiple, bulging

16 Angiomyolipoma

17 M 8860/1

18 Benign Kidney Tumours Mimicking Carcinomas and Sarcomas Metanephric adenoma - large & cellular Oncocytoma Angiomyolipoma - large with atypiae - large with atypiae

19 Epithelial Kidney Tumours malignant CARCINOMAS Clear Conventional Cell Papillary (chromophillic) type 1 type 2 Chromophobe classical eosinophillic Sarcomatoid Cystic Collecting Duct

20 Clear Cell Renal Cell Carcinoma ccrcc (Grawitz tumour) Solid / cystic Unilocullar or multilocular Micro - solid or tubulocystic clear cytoplasm (fat & glycogen) Immunohistochemistry RCC, cytokeratins, vimentin, CD10, EMA, S-100 Cytogenetics deletion of the short arm chromosome 3 (3p25) VHL gene Prognosis: G, pt dependent Sarcomatoid variant is the most malignant

21 WHO 2016

22 Clear cell carcinoma Grawitz tumour

23 capsular invasion Clear Cell Ca M 8310/3 M 54

24 Clear Cell Renal Cell Ca M 8310/3 PAS

25 Clear Cell Renal Cell Ca M 8310/3

26 Metastasis ccrcc Adrenal

27 Clear Cell Renal Cell Ca, G4 M 8310/3

28 Papillary (Chromophillic) Ca M 8260/3 10% In dialysed more frequent; can be multifocal and bilateral X-ray hypovascular Histology papillary/ tubulopapillary type 1 cubic cells type 2 - cylindric cells (worse prognosis) Genetics trisomy or tetrasomy 7 and 17 in men often Y chromosome missing mutation of c-met oncogen Prognosis : G, pt dependent slightly better than in conventional ca

29 Ca papillare renis sin. F42

30 Papillary ca M68

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33 Chromophobe Carcinoma M 8317/3 5% Macro Mikro Elmi - brown color - solid, cytoplasms clear or eosinophillic positive in Hale s colloidal iron staining raisin-like cell nuclei microvesicles in cytoplasm Genetics missing chromosomes - 1, 2, 10, 13, 6, 21, 17 Prognosis: G, pt dependent

34 Ca chromophobum renis

35 Chromophobe Carcinoma M 8317/3

36 Chromophobe Carcinoma M 8317/3 ale s colloidal Fe

37 Collecting Duct Carcinoma Starts in the medulla Micro adenocarcinoma & urothelial like hobnail cells papillary fibroplasia, mucin production Imuno Prognosis unfavourable cytokeratin 13, vimentin, lectin

38 Nephroblastoma (Wilms tumour) M 8960/3 syn. - embryonal adenosarcoma Children - preschool age Macro: gray-white large retroperitoneal mass palpable through abdominal wall Micro: undifferentiated renal blastema, tubular and glomeruloid formations may be present Prognosis: curable (stage!) resection and chemotherapy Follow up: - nephrogenic rests

39 Nephroblastoma (Wilms tumour) M 8960/3 Genetics WAGR syndrome Wilms-Aniridia-Genital Anomaly-Retardation Denys Drash syndrome DDS - gonadal dysgenesis and renal abnormalities inactivation of the WT 1 gene Beckwith Wiedeman syndrome BWS - organomegaly ( tongue, kidney, liver, hemihypertrophy) loss of silencing of maternal IGF 2 gene

40 Nephroblastoma Wilms tumour M8960/3

41 Nephroblastoma Wilms tumour

42 Nephroblastoma is not a single tumour, but a family with different behaviour classification reflects different clinical course and therapeutic response WHO 4th ed. 2016

43 Factors with an Adverse Prognosis Influence in Kidney Cancer Size Invasion to venes Grading Staging Proliferation Index p53 Expression diam. more than 12 cm recurrences G III and G IV most important

44 Kidney Cancer complications 1. metastatic spread & generalisation manifestation via solitary bloodborne metastasis possible (pathological fracture, struma neoplastica ) hematuria anemia

45 Kidney Cancer complications 2. hormon production erythropoietin polyglobulia Wood L, Swanepoel C, du Toit A, Jacobs P. Clinically silent renal tumour producing erythropoietin. S Afr Med J Feb;93(2): Shaheen M, Hilgarth KA, Hawes D, Badve S, Antony AC. A Mexican man with "too much blood". Lancet Sep 6;362(9386):806. insulin, glucagon, renin, PTH like substances

46 Tumours of the urinary tract WHO 4th ed. 2016

47 Tumours of the urinary tract

48 Urothelial Cancer approx. 3% of total human cancer burden increasing incidence industrialized countries risk factors: TOBACCO SMOKING aniline dye industry phenacetin schistosomiasis

49 Carcinoma vesicae urinariae M8120/3, G3, pt3b, pn2, pmx Carcinoma vesicae urinariae M 60

50 Symptoms hematuria (obstruction) (metastases)

51 Terminology the term UROTHELIAL be used rather than transitional...

52 Normal urothelium multilayered variable number of layers empty bladder 4-6 full bladder 2-3 Cells: basal superficial ( umbrella ) neuroendocrine polyploid, binuclear

53 lamina muscularis mucosae urothelium contracted bladder Norma vessels

54 Variations of Urothelium slight reactive changes von Brunn s nests mucinous metaplasia squamous metaplasia (nonkeratinising, vagina type)

55 von Brunn s Nests

56 HG IUN von Brunn s Nests

57 von Brunn s Nests mucinous metaplasia - alc. blue ph2,5

58 Squamous cell metaplasia

59 Hyperplasia Def: regular increase in number of uroth. layers (min. >7, mostly >10) slight increase in cell nuclei size, preserved architecture

60 Flat hyperplasia

61 Papillary hyperplasia

62 Hyperplasia Significance: precancerosis 70% of patients with urothelial ca identical mutations (mostly 9q deletion like in low grade papillary tumours)

63 Flat lesions with atypia Reactive (inflammatory) atypia Atypia of unknown significance Dysplasia (LG IUN) CIS (HG IUN) Mild reactive changes

64 Dysplasia DEF: disturbance of normal urothelium architecture & cytology

65 Dysplasia LG IUN low grade intraurothelial neoplasia HG IUN/ CIS high grade intraurothelial neoplasia / CARCINOMA IN SITU

66 LG IUN mild dysplasia norm

67 HG IUN moderate dysplasia

68 Papillary neoplasms Papilloma Inverted papilloma Papillary Urothelial Neoplasm of Low Malignant Potential PUNLMP Papillary carcinoma, low grade Papillary carcinoma, high grade

69 Papilloma WHO 1973 G0 Def: circumscribed solitary papillary lesion covered with cytologically and architecturally normal urothelium.

70 Papillary Urotelial Neoplasm of Low Malignant Potential - PUNLMP Def.: well stratified urothelium bearing features of minimal atypia and increased number of layers

71 Urothelial papillocarcinoma

72 Papillary carcinoma low grade G2

73 Urothelial carcinoma

74 Urothelial papillocarcinoma

75 Papillary ca HG (G2)

76 Invasive neoplasms lamina propria invasion (pt1a,b) muscularis propria (detrusor muscle) invasion (pt2a,b) perivesical tissue macro/micro (pt3a,b) surrounding organs/ abdominal wall (pt4a,b)

77 pt1a

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79 Ca urotheliale invasivum

80 WHO 4th ed Tumours of the urinary tract STAGING

81 Papillary ca high grade G3, pt2

82 Less Common Types of Urinary Bladder Cancer microcystic carcinoma with pseudosarcomatose stroma with bone or chondroid stromal metaplasia spinocellular adenocarcinoma undifferenciated ca with trophoblastic differentiation neuroendocrine

83 Microcystic carcinoma

84 Neuroendocrine carcinoma

85 Non-Epithelial Bladder Tumours - Mesenchymal leiomyomas and leiomyosarcomas rhabdomyosarcoma vascular (capillary, cavernous and angiovenous) hemangiomas and hemangiosarcomas malignant lymphomas

86 Non-Epithelial Bladder Tumours - Neuroectodermal neurofibromas in Recklinghausen s disease melanoma, naevus, melanosis paraganglioma

87 Urinary Bladder Pseudotumors inflammatory malakoplakia amyloid deposits

88 Cystectomy biopsy report Microscopy: type, grade (G) and stage (pt) of the tumor further urothelial abnormities lymphatic and blood vessel invasion presence / absence of the tumor in the resection margins and neighbouring organs further abnormities of the neighbouring organs

89 Urinary Tract Cancer - complications local recurrences - regular follow up incl. urinary cytology progression metastases

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